C-reactive protein (CRP), the prototype human acute phase reactant, facilitates human B cell colony responses stimulated by Staph protein A (SpA) in semisolid cultures. By contrast the promotion of B cell colony responses during the autologous mixed lymphocyte reaction (MLR) is impaired by moderate concentrations of CRP. Preliminary studies show that about 13% of monocytes from patients with rheumatoid arthritis bear CRP. The characteristics of human B cell colony responses and their usefulness in detecting and evaluating the immunoregulatory role of soluble mediators have been demonstrated. The first phase of the proposed studies will investigate the mechanisms by which CRP enhances B cell colony responses when monocytes are present. By flow microcytofluorometry (FMF) we will determine if the pre-exposure of monocytes and B cells to CRP alters the expression of HLA-DR and other phenotypic markers on both cell types since their presence correlates with optimal colony responses. In parallel experiments we will examine whether CRP alters the release of interleukin 1 (IL-1), it biological activity or the sensitivity of B cells to 11-1. The second series of experiments will analyze the mechanisms responsible for CRP-mediated inhibition of the facilitation of colony responses induced by an autologous MLR. The possible mechanisms include effects on: i) autoreactive responder T cell subsets of the OKT series, ii) autohelper stimulatory B cells and monocytes and/or iii) B cell colony progenitors recruited into the colony forming pool during the course of an autologous MLR. In conjunction with the evaluation of CRP on functional activities, the binding of CRP to distinct lymphocyte and monocyte subpopulations will be determined both by FMF and with radiolabeled CRP. The last series of experiments will focus on the functional activities of CRP bearing mononuclear cells from patients with rheumatoid arthritis in comparison with identical cells from patients and normals which do not bear CRP. We expect that the outcome of these experiments will define the role of CRP in modulating immune responsiveness. Such information should contribute to our knowledge of the immunpathogenesis of rheumatoid arthritis and may eventually form the basis for a more specific therapeutic strategy.